TY - JOUR
T1 - Investigating PUM1 mutations in a Taiwanese cohort with cerebellar ataxia
AU - Lai, Kuan Lin
AU - Liao, Yi Chu
AU - Tsai, Pei Chien
AU - Soong, Bing Wen
AU - Lee, Yi Chung
N1 - Funding Information:
This work was supported by the grants from Ministry of Science and Technology, Taiwan , ROC [MOST 107-2314-B-075-014-MY3 ], and Taipei Veterans General Hospital [ V108B-035 , V108C-011 ]. This work was also financially supported by the Brain Research Center, National Yang-Ming University from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan .
Publisher Copyright:
© 2019 Elsevier Ltd
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019/9
Y1 - 2019/9
N2 - Introduction: Mutations in the PUM1 gene were recently identified to cause spinocerebellar ataxia type 47 (SCA47). However, their role in cerebellar ataxia in various populations remains elusive. The aim of this study was to elucidate the frequency and spectrum of PUM1 mutations in a cohort of Taiwanese patients with molecularly undetermined cerebellar ataxia. Methods: Mutational analyses of PUM1 were performed by Sanger sequencing in a cohort of 248 unrelated patients with cerebellar ataxia of unknown cause, including 108 with autosomal-dominantly inherited cerebellar ataxia, 45 with autosomal-recessively inherited cerebellar ataxia, and 95 with apparently sporadic cerebellar ataxia. Among them, the genetic causes of ataxia remained unknown after excluding mutations responsible for SCA1, 2, 3, 6, 7, 8, 10, 12, 17, 19/22, 23, 26, 27, 28, 31, 35, 36, dentatorubral-pallidoluysian atrophy and Friedreich's ataxia. Results: Two heterozygous missense PUM1 variants were identified in two patients with apparently sporadic cerebellar ataxia, including a known disease-causing mutation (p.R1139W) and a variant of uncertain significance (p.K151R). The patient carrying the p.R1139W mutation had a slowly progressive, relatively pure cerebellar ataxia, presenting with gait unsteadiness, limb dysmetria, ataxic dysarthria and saccadic pursuit. Conclusion: Our findings support the pathogenic role of PUM1 mutations in cerebellar ataxia and emphasize the importance of considering PUM1 mutations as a possible etiology of cerebellar ataxia.
AB - Introduction: Mutations in the PUM1 gene were recently identified to cause spinocerebellar ataxia type 47 (SCA47). However, their role in cerebellar ataxia in various populations remains elusive. The aim of this study was to elucidate the frequency and spectrum of PUM1 mutations in a cohort of Taiwanese patients with molecularly undetermined cerebellar ataxia. Methods: Mutational analyses of PUM1 were performed by Sanger sequencing in a cohort of 248 unrelated patients with cerebellar ataxia of unknown cause, including 108 with autosomal-dominantly inherited cerebellar ataxia, 45 with autosomal-recessively inherited cerebellar ataxia, and 95 with apparently sporadic cerebellar ataxia. Among them, the genetic causes of ataxia remained unknown after excluding mutations responsible for SCA1, 2, 3, 6, 7, 8, 10, 12, 17, 19/22, 23, 26, 27, 28, 31, 35, 36, dentatorubral-pallidoluysian atrophy and Friedreich's ataxia. Results: Two heterozygous missense PUM1 variants were identified in two patients with apparently sporadic cerebellar ataxia, including a known disease-causing mutation (p.R1139W) and a variant of uncertain significance (p.K151R). The patient carrying the p.R1139W mutation had a slowly progressive, relatively pure cerebellar ataxia, presenting with gait unsteadiness, limb dysmetria, ataxic dysarthria and saccadic pursuit. Conclusion: Our findings support the pathogenic role of PUM1 mutations in cerebellar ataxia and emphasize the importance of considering PUM1 mutations as a possible etiology of cerebellar ataxia.
KW - Cerebellar ataxia
KW - PUM1
KW - Pumilio1
KW - SCA47
KW - Spinocerebellar ataxia
UR - http://www.scopus.com/inward/record.url?scp=85070566789&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85070566789&partnerID=8YFLogxK
U2 - 10.1016/j.parkreldis.2019.08.004
DO - 10.1016/j.parkreldis.2019.08.004
M3 - Article
C2 - 31422002
AN - SCOPUS:85070566789
SN - 1353-8020
VL - 66
SP - 220
EP - 223
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
ER -